Cathepsin B is a representative of the papain-like cysteine peptidase family. Its structure is different from the other representatives of this family, in that it has an additional structural element called the occluding loop. This element allows it to act as an endo- or exopeptidase. Endopeptidase activity of cathepsin B is involved in various pathological conditions, such as rheumatic diseases.
In thesis, we tested the effects of selected amino acid derivatives of succinimide on the activity of human cathepsin B. We determined residual enzyme activity at saturation with inhibitors and the potency of the inhibitors expressed as EC50 were determined. From our in-house compound library, we identified compounds 6, 8 and 15, as partial inhibitors of cathepsin B and compounds 4, 5, 11 and 12 as linear inhibitors, respectively. Selected inhibitors were also assayed for their inhibitory effect on the hydrolysis of the macromolecular substrate azocaseins. Partial inhibitors, for the most part, retained their inhibitory activity, whereas linear inhibitors did not significantly affect the caseinolytic activity of cathepsin B.
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